# # # Helper module for Bio::SeqIO::game::featHandler # # Please direct questions and support issues to # # Cared for by Sheldon McKay # # You may distribute this module under the same terms as perl itself # # POD documentation - main docs before the code =head1 NAME Bio::SeqIO::game::featHandler -- a class for handling feature elements =head1 SYNOPSIS This module is not used directly =head1 DESCRIPTION Bio::SeqIO::game::featHandler converts game XML EannotationE elements into flattened Bio::SeqFeature::Generic objects to be added to the sequence =head1 FEEDBACK =head2 Mailing Lists User feedback is an integral part of the evolution of this and other Bioperl modules. Send your comments and suggestions preferably to one of the Bioperl mailing lists. Your participation is much appreciated. bioperl-l@bioperl.org - General discussion http://bioperl.org/wiki/Mailing_lists - About the mailing lists =head2 Support Please direct usage questions or support issues to the mailing list: I rather than to the module maintainer directly. Many experienced and reponsive experts will be able look at the problem and quickly address it. Please include a thorough description of the problem with code and data examples if at all possible. =head2 Reporting Bugs Report bugs to the Bioperl bug tracking system to help us keep track of the bugs and their resolution. Bug reports can be submitted via the web: https://redmine.open-bio.org/projects/bioperl/ =head1 AUTHOR - Sheldon McKay Email mckays@cshl.edu =head1 APPENDIX The rest of the documentation details each of the object methods. Internal methods are usually preceded with a _ =cut package Bio::SeqIO::game::featHandler; use Bio::SeqFeature::Generic; use Bio::Location::Split; use Data::Dumper; use strict; use vars qw {}; use base qw(Bio::SeqIO::game::gameSubs); =head2 new Title : new Usage : my $featHandler = Bio::SeqIO::game::featHandler->new($seq, $seq_h, $ann_l) Function: creates an object to deal with sequence features Returns : a handler object Args : $seq -- a Bio::SeqI compliant object $seq_h -- ref. to a hash of other sequences associated with the main sequence (proteins, etc) $ann_l -- ref. to a list of annotations =cut sub new { my ($caller, $seq, $seq_h, $ann_l ) = @_; my $class = ref($caller) || $caller; my $self = bless ({ seq => $seq, curr_feats => [], curr_coords => [], seq_h => $seq_h, ann_l => $ann_l, }, $class); return $self; } =head2 add_source Title : add_source Usage : $featHandler->add_source($seq->length, \%tags); Function: creates a source feature Returns : a Bio::SeqFeature::Generic object Args : sequence length and a ref. to a hash of tag/value attributes =cut sub add_source { my ($self, $length, $tags) = @_; my $feat = Bio::SeqFeature::Generic->new( -primary => 'source', -start => 1, -end => $length, ); for ( keys %{$tags} ) { for my $val ( @{$tags->{$_}} ) { $feat->add_tag_value( $_ => $val ); } } return $feat; } =head2 has_gene Title : has_gene Usage : my $gene = $self->_has_gene($gene, $gname, $id) Function: method to get/set the current gene feature Returns : a Bio::SeqFeature::Generic object (if there is a gene) Args : (optional) $gene -- an XML element for the annotation $gname -- gene name $id -- gene ID (not always the same as the name) =cut sub has_gene { my ($self, $gene, $gname, $id) = @_; # use name preferentially over id. We can't edit IDs in Apollo # AFAIK, and this will create an orphan CDS for newly created # transcipts -- I think this needs more work #$id = $gname if $id && $gname; unless ( $gene ) { if ( defined $self->{curr_gene} ) { return $self->{curr_gene}; } else { return 0; } } else { if ( $id && !$self->{curr_ltag} ) { $self->{curr_ltag} = $id; } if ( $gname && !$self->{curr_gname} ) { $self->{curr_gname} = $gname; } my $tags = {}; for my $child ( @{$gene->{Children}} ) { my $name = $child->{Name}; if ( $name eq 'dbxref' ) { $tags->{dbxref} ||= []; push @{$tags->{dbxref}}, $self->dbxref( $child ); } elsif ( $name !~ /name/ ){ $self->complain("Unrecognized element '$name'. I don't " . "know what to do with $name elements"); } } my $feat = Bio::SeqFeature::Generic->new( -primary => 'gene', ); my %seen; for ( keys %{$tags} ) { for my $val ( @{$tags->{$_}} ) { $feat->add_tag_value( $_ => $val ) unless ++$seen{$_.$val} > 1; } } $self->{curr_gene} = $feat; return $feat; } } =head2 _has_CDS Title : _has_CDS Usage : my $cds = $self->_has_CDS Function: internal getter/setter for CDS features Returns : a Bio::SeqFeature::Generic transcript object (or nothing) Args : a Bio::SeqFeature::Generic transcript feature =cut sub _has_CDS { my ($self, $transcript) = @_; if ( !$transcript ) { if ( defined $self->{curr_cds} ) { return $self->{curr_cds}; } else { return 0; } } else { my $tags = $self->{curr_tags}; $self->{curr_cds} = $self->_add_CDS( $transcript, $tags ); } } =head2 add_annotation Title : add_annotation Usage : $featHandler->add_annotation($seq, $type, $id, $tags, $feats) Function: converts a containment hierarchy into an ordered list of flat features Returns : nothing Args : $seq -- a Bio::SeqI compliant object $type -- the annotation type $id -- the anotation ID $tags -- ref. to a hash of tag/value attributes $feats -- ref to an array of Bio::SeqFeature::Generic objects =cut sub add_annotation { my ($self, $seq, $type, $id, $tags, $feats) = @_; # is this a generic feature? unless ( $self->has_gene ) { shift; $self->_add_generic_annotation(@_); return 0; } my $feat; if ( $type eq 'gene' ) { $feat = $self->has_gene; $feat->add_tag_value( gene => ($self->{curr_gname} || $id) ) unless $feat->has_tag('gene'); } else { $feat = Bio::SeqFeature::Generic->new; $feat->primary_tag($type); my $gene = $self->has_gene; $gene->add_tag_value( gene => ($self->{curr_gname} || $id) ) unless $gene->has_tag('gene'); $feat->add_tag_value( gene => ($self->{curr_gname} || $id) ) unless $feat->has_tag('gene');; } for ( keys %{$tags} ) { # or else add simple tag/value pairs if ( $_ eq 'name' && $tags->{type}->[0] eq 'gene' ) { $feat->add_tag_value( gene => $tags->{name}->[0] ) unless $feat->has_tag( 'gene' ); delete $tags->{name}; } else { next if $_ eq 'type' && $tags->{$_}->[0] eq 'gene'; next if $_ eq 'gene' && $feat->has_tag( 'gene' ); for my $val ( @{$tags->{$_}} ) { $feat->add_tag_value( $_ => $val ); } } } $feat->strand( $self->{curr_strand} ); $feat->start( $self->{curr_coords}->[0] ); $feat->end( $self->{curr_coords}->[1] ); # create an array of features for the annotation (order matters) my @annotations = ( $feat ); # add the gene feature if the annotation is not a gene if ( $self->has_gene && $type ne 'gene') { my $gene = $self->has_gene; $gene->strand( $self->{curr_strand} ); $gene->start( $self->{curr_coords}->[0] ); $gene->end( $self->{curr_coords}->[-1] ); push @annotations, $gene; $self->{curr_gene} = ''; } # add the subfeatures for ( @{$feats} ) { $self->complain("bad feature $_") unless ref($_) =~ /Bio/; push @annotations, $_; } # add the annotation array to the list for this sequence my $seqid = $seq->id; my $list = $self->{ann_l}; # make sure the feature_sets appear in ascending order if ( $list->[0] && $annotations[0]->start < $list->[0]->start ) { unshift @{$list}, @annotations; } else { push @{$list}, @annotations; } # garbage collection $self->{curr_gene} = ''; $self->{curr_ltag} = ''; $self->{curr_gname} = ''; $self->{curr_coords} = []; $self->{curr_feats} = []; $self->{curr_strand} = 0; $self->{ann_seq} = $seq; $self->flush; } =head2 _add_generic_annotation Title : _add_generic_annotation Usage : $self->_add_generic_annotation($seq, $type, $id, $tags, $feats) Function: an internal method to handle non-gene annotations Returns : nothing Args : $seq -- a Bio::SeqI compliant object $type -- the annotation type $id -- the anotation ID $tags -- ref. to a hash of tag/value attributes $feats -- ref to an array of Bio::SeqFeature::Generic objects =cut sub _add_generic_annotation { my ($self, $seq, $type, $id, $tags, $feats) = @_; for ( @$feats ) { $_->primary_tag($type); } push @{$self->{ann_l}}, @$feats; $self->{curr_coords} = []; $self->{curr_feats} = []; $self->{curr_strand} = 0; $self->{ann_seq} = $seq; $self->flush; } =head2 feature_set Title : feature_set Usage : push @feats, $featHandler->feature_set($id, $gname, $set, $anntype); Function: handles hierarchies (usually a transcript) Returns : a list of Bio::SeqFeature::Generic objects Args : $id -- ID of the feature set $gname -- name of the gene $set -- the object $anntype -- type of the parent annotation =cut sub feature_set { my ($self, $id, $gname, $set, $anntype) = @_; my $stype = $set->{_type}->{Characters}; $self->{curr_loc} = []; $self->{curr_tags} = {}; $self->{curr_subfeats} = []; $self->{curr_strand} = 0; my @feats = (); my $tags = $self->{curr_tags}; my $sname = $set->{_name}->{Characters} || $set->{Attributes}->{id}; if ( $set->{Attributes}->{problem} ) { $tags->{problem} = [$set->{Attributes}->{problem}]; } my @fcount = grep { $_->{Name} eq 'feature_span' } @{$set->{Children}}; if ( @fcount == 1 ) { $self->_build_feature_set($set, 1); my ($feat) = @{$self->{curr_subfeats}}; $feat->primary_tag('transcript') if $feat->primary_tag eq 'exon'; if ( $feat->primary_tag eq 'transcript' ) { $feat->add_tag_value( gene => ($gname || $id) ) unless $feat->has_tag('gene'); } my %seen_tag; for my $tag ( keys %{$tags} ) { for my $val ( @{$tags->{$tag}} ) { $feat->add_tag_value( $tag => $val ) if $val && ++$seen_tag{$tag.$val} < 2; } } @feats = ($feat); } else { $self->{curr_ltag} = $id; $self->{curr_cds} = ''; $gname = $id if $gname eq 'gene'; $self->{curr_gname} = $gname; if ( $self->has_gene ) { unless ( $anntype =~/RNA/i ) { $stype =~ s/transcript/mRNA/; } } $self->{curr_feat} = Bio::SeqFeature::Generic->new( -primary => $stype, -id => $id, ); my $feat = $self->{curr_feat}; $self->_build_feature_set($set); my $gene = $gname || $self->{curr_ltag}; $feat->add_tag_value( gene => $gene ) unless $feat->has_tag('gene'); # if there is an annotated protein product my $cds = $self->_has_CDS( $feat ); if ( $cds ) { $feat->primary_tag('mRNA'); # we really just want one value here $cds->remove_tag('standard_name') if $cds->has_tag('standard_name'); $cds->add_tag_value( standard_name => $sname ); $cds->remove_tag('gene') if $cds->has_tag('gene'); $cds->add_tag_value( gene => $gene ); # catch empty protein ids if ( $cds->has_tag('protein_id' ) && !$cds->get_tag_values('protein_id') ) { my $pid = $self->protein_id($cds, $sname); $cds->remove_tag('protein_id'); $cds->add_tag_value( protein_id => $pid ); } # make sure other subfeats are tied to the transcript # via a 'standard_name' qualifier and the gene via a 'gene' qualifier my @subfeats = @{$self->{curr_subfeats}}; for my $sf ( @ subfeats ) { $sf->add_tag_value( standard_name => $sname ) unless $sf->has_tag('standard_name'); $sf->add_tag_value( gene => $gene ) unless $sf->has_tag('gene'); } $feat->add_tag_value( standard_name => $sname ) unless $feat->has_tag('standard_name'); $feat->add_tag_value( gene => $gene ) unless $feat->has_tag('gene'); # if the mRNA and CDS are the same length, the mRNA is redundant # lose the mRNA, steal its tags and give them to the CDS my %seen; if ( $feat->length == $cds->length ) { for my $t ( $feat->all_tags ) { next if $t =~ /gene|standard_name/; $cds->add_tag_value( $t => $feat->get_tag_values($t) ); } undef $feat; } @feats = sort { $a->start <=> $b->start } ($cds, @subfeats); unshift @feats, $feat if $feat; } else { if ( @{$self->{curr_loc}} > 1 ) { my $loc = Bio::Location::Split->new( -splittype => 'JOIN' ); # sort the exons in ascending start order my @loc = sort { $a->start <=> $b->start } @{$self->{curr_loc}}; # then add them to the transcript location for ( @loc ) { $loc->add_sub_Location( $_ ) } $feat->location( $loc ); } else { $feat->location( $self->{curr_loc}->[0] ); } for ( keys %$tags ) { # expunge duplicate gene attributes next if /gene/ && $feat->has_tag('gene'); for my $v ( @{$tags->{$_}} ) { $feat->add_tag_value( $_ => $v ); } } # make sure other subfeats are tied to the transcript my @subfeats = @{$self->{curr_subfeats}}; for my $sf ( @ subfeats ) { $sf->add_tag_value( standard_name => $sname ) unless $sf->has_tag('standard_name'); $sf->add_tag_value( gene => $gene ) unless $sf->has_tag('gene'); } @feats = ( $feat, @subfeats ); } } # adjust the maximum extent of the annotated feature # if req'd (ie the element) $self->{curr_coords}->[0] ||= 1000000000000; $self->{curr_coords}->[1] ||= -1000000000000; for ( @feats ) { if ( $self->{curr_coords}->[0] > $_->start ) { $self->{curr_coords}->[0] = $_->start; } if ( $self->{curr_coords}->[1] < $_->end ) { $self->{curr_coords}->[1] = $_->end; } } $self->flush( $set ); return @feats; } =head2 _build_feature_set Title : _build_feature_set Usage : $self->_build_feature_set($set, 1) # 1 flag means retain the exon as a subfeat Function: an internal method to process attributes and subfeats of a feature set Returns : nothing Args : $set -- a element 1 -- optional flag to retain exons as subfeats. Otherwise, they will be converted to sublocations of a parent CDS feature =cut sub _build_feature_set { my ($self, $set, $keep_subfeat) = @_; for my $child ( @{$set->{Children}} ) { my $name = $child->{Name}; # these elements require special handling if ( $name eq 'date' ) { $self->date( $child ); } elsif ( $name eq 'comment' ) { $self->comment( $child ); } elsif ( $name eq 'evidence' ) { $self->evidence( $child ); } elsif ( $name eq 'feature_span' ) { $self->_add_feature_span( $child, $keep_subfeat ); } elsif ( $name eq 'property' ) { $self->property( $child ); } # need to add the db_xref tags to the gene? # otherwise, simple tag/value pairs elsif ( $name =~ /synonym|author|description/) { $self->{curr_tags}->{$name} = [$child->{Characters}]; } elsif ( $name !~ /name|type|seq/ ){ $self->complain("Unrecognized element '$name'. I don't " . "know what to do with $name elements"); } } } =head2 _add_feature_span Title : _add_feature_span Usage : $self->_add_feature_span($el, 1) Function: an internal method to process elements Returns : nothing Args : $el -- a element 1 -- an optional flag to retain exons as subfeatures =cut sub _add_feature_span { my ($self, $el, $keep_subfeat) = @_; my $tags = $self->{curr_tags}; my $feat = $self->{curr_feat}; my $type = $el->{_type}->{Characters} || $el->{Name}; my $id = $el->{Attributes}->{id} || $el->{_name}->{Characters}; my $seqr = $el->{_seq_relationship}; my $start = int $seqr->{_span}->{_start}->{Characters}; my $end = int $seqr->{_span}->{_end}->{Characters}; my $stype = $seqr->{Attributes}->{type}; my $seqid = $seqr->{Attributes}->{seq}; push @{$self->{seq_l}}, $self->{seq_h}->{$seqid}; if ( $start > $end ) { $self->{curr_strand} = -1; ($start, $end) = ($end, $start); } else { $self->{curr_strand} = 1; } # add exons to the transcript if ( $type eq 'exon' ) { my $sl = Bio::Location::Simple->new( -start => $start, -end => $end, -strand => $self->{curr_strand} ); push @{$self->{curr_loc}}, $sl; } # apollo and gadfly use different tags for the same thing if ( $type =~ /start_codon|translate offset/ ) { $self->{curr_tags}->{codon_start} = [$start]; } else { if ( $type eq 'exon' ) { return unless $keep_subfeat; } push @{$self->{curr_subfeats}}, Bio::SeqFeature::Generic->new( -start => $start, -end => $end, -strand => $self->{curr_strand}, -primary => $type ); } # identify the translation product my $tscript = $el->{Attributes}->{produces_seq}; if ( $tscript && $tscript ne 'null') { my $subseq = $self->{seq_h}->{$el->{Attributes}->{produces_seq}}; $self->{curr_tags}->{product} = [$el->{Attributes}->{produces_seq}]; $self->{curr_tags}->{translation} = [$subseq->seq] if $subseq; } $self->flush( $el ); } =head2 _add_CDS Title : _add_CDS Usage : my $cds = $self->_add_CDS($transcript, $tags) Function: an internal method to create a CDS feature from a transcript feature Returns : a Bio::SeqFeature::Generic object Args : $transcript -- a Bio::SeqFeature::Generic object for a transcript $tags -- ref. to a hash of tag/value attributes =cut sub _add_CDS { my ($self, $feat, $tags) = @_; my $loc = {}; my $single = 0; if ( @{$self->{curr_loc}} > 1 ) { $loc = Bio::Location::Split->new; # sort the exons in ascending start order my @loc = sort { $a->start <=> $b->start } @{$self->{curr_loc}}; # then add them to the location object for ( @loc ) { $loc->add_sub_Location( $_ ); } } else { $loc = $self->{curr_loc}->[0]; $single++; } # create a CDS my @exons = $single ? $loc : $loc->sub_Location(1); $feat->location($loc); # try to find a peptide my $seq = $self->{seq_h}->{ $tags->{protein_id}->[0] }; $seq ||= $self->{seq_h}->{ $tags->{product}->[0] } || $self->{seq_h}->{ $tags->{gene}->[0] } || $self->{seq_h}->{ $tags->{standard_name}->[0] }; # Can we count on the description format being consistent? # Why is CDS coordinate info saved as description text not # specified in the DTD? Anyone have a better idea? Aww, # who am I kidding, I'm the only one who will ever read this! my ($start, $stop, $peptide) = (); if ( $seq ) { $peptide = $seq->display_id; my $desc = $seq->description || ''; $desc =~ s/,|\n//g; $desc =~ s/\)(\w)/\) $1/g; if ( $desc =~ /cds_boundaries:.+?(\d+)\.\.(\d+)/ ) { ($start, $stop) = ($1 - $self->{offset}, $2 - $self->{offset}); } else { # OK, I guess the transcript must be the CDS then $start = $loc->start; $stop = $loc->end; } } else { $self->warn("I did not find a protein sequence for " . $feat->display_name); } delete $tags->{transcript}; # now chop off the UTRs to create a CDS my @exons_to_add = (); #warn scalar(@exons), " exons, $start, $stop\n"; for ( @exons ) { my $exon = Bio::Location::Simple->new; if ( $_->end < $start || $_->start > $stop ) { #warn "exon out of range\n"; next; } if ( $_->start < $start && $_->end > $start ) { #warn "chopping off left UTR\n"; $exon->start( $start ); } if ( $_->end > $stop && $_->start < $stop ) { #warn "chopping off right UTR\n"; $exon->end( $stop ); } unless ($exon->valid_Location) { $exon->start( $_->start ); $exon->end( $_->end ); } $exon->strand ( $self->{curr_strand} ); push @exons_to_add, $exon; } my $cds_loc; if ( @exons_to_add > 1 ) { $cds_loc = Bio::Location::Split->new( -splittype => 'JOIN' ); for ( @exons_to_add ) { $cds_loc->add_sub_Location( $_ ); } } else { $cds_loc = $exons_to_add[0]; } my $parent = $self->{curr_gname} || $self->{curr_ltag}; # try not to steal too many mRNA attributes for the CDS my $cds_tags = {}; for my $k ( keys %$tags ) { if ( $k =~ /product|protein|translation|codon_start/ ) { $cds_tags->{$k} = $tags->{$k}; delete $tags->{$k}; } } for ( keys %$tags ) { for my $v ( @{$tags->{$_}} ) { $feat->add_tag_value( $_ => $v ) unless $feat->has_tag($_); } } if ( $self->{curr_gname} ) { $cds_tags->{gene} = [$self->{curr_gname}]; } my $gene = $self->has_gene; my $cds = Bio::SeqFeature::Generic->new( -primary => 'CDS', -location => $cds_loc, ); $cds_tags->{translation} = [$seq->seq]; for ( keys %{$cds_tags} ) { my %seen; for my $val (@{$cds_tags->{$_}}) { next if ++$seen{$val} > 1; $cds->add_tag_value( $_ => $val ); } } $cds; } 1;